The film is the sequel to the 2010 hit Machete, starring Danny Trejo as the title character.

Trejo returns for the sequel along with co-stars Michelle Rodriguez and Jessica Alba. They are joined by newcomers to the series Charlie Sheen (as the U.S. president), Mel Gibson (as an arms dealer), Edward James Olmos, Lady Gaga, Vanessa Hudgens, Sofia Vergara, Alexa Vega, Cuba Gooding Jr., William Sadler, Heard, Zoe Saldana, and Demian Bechir.